In Vivo Tropism of Attenuated and Pathogenic Measles Virus Expressing Green Fluorescent Protein in Macaques
In Vivo Tropism of Attenuated and Pathogenic Measles Virus Expressing Green Fluorescent Protein in Macaques
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DOI：
10.1128/jvi.02633-09
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发表时间：
2010-05-01
影响因子：
5.4
通讯作者：
Duprex, W. Paul
中科院分区：
文献类型：
--
作者：
de Vries, Rory D.;Lemon, Ken;Duprex, W. Paul
全球麻疹疫苗接种的增加导致麻疹死亡率显着降低。减毒活麻疹病毒（MV）疫苗的标准给药途径是皮下注射，尽管其他无针途径（包括气雾剂给药）正在研究中。在体外，减毒 MV 比临床分离株具有更广泛的趋向性，因为它可以使用 CD46 和 CD150 作为细胞受体。为了比较减毒和致病性MV的体内趋向性，我们通过气管内或气溶胶途径用表达增强型绿色荧光蛋白（GFP）的致病性或减毒重组MV（分别为IC323和Edmonston菌株）感染食蟹猴。令人惊讶的是，无论给药途径如何，这两种病毒在肺部的病毒载量和细胞向性都相似，并且 CD11c 阳性细胞被确定为主要目标群体。然而，只有致病性MV引起显着的病毒血症，导致淋巴组织中的B和T淋巴细胞中病毒大量复制，并导致病毒传播至皮肤和呼吸道上皮粘膜下层。减毒的 MV 很少在淋巴组织中检测到，即使检测到，也仅在分离的感染细胞中检测到。吸入气溶胶后，在上呼吸道的早期时间点检测到减弱的 MV，表明局部病毒复制。这与致病性MV形成对比，致病性MV仅在病毒血症发生后才侵入上呼吸道。这项研究表明，尽管体外存在差异，但减毒和致病性 MV 在肺部表现出高度相似的体内趋向性。然而，减毒MV的系统性传播受到限制。
The global increase in measles vaccination has resulted in a significant reduction of measles mortality. The standard route of administration for the live-attenuated measles virus (MV) vaccine is subcutaneous injection, although alternative needle-free routes, including aerosol delivery, are under investigation. In vitro, attenuated MV has a much wider tropism than clinical isolates, as it can use both CD46 and CD150 as cellular receptors. To compare the in vivo tropism of attenuated and pathogenic MV, we infected cynomolgus macaques with pathogenic or attenuated recombinant MV expressing enhanced green fluorescent protein (GFP) (strains IC323 and Edmonston, respectively) via the intratracheal or aerosol route. Surprisingly, viral loads and cellular tropism in the lungs were similar for the two viruses regardless of the route of administration, and CD11c-positive cells were identified as the major target population. However, only the pathogenic MV caused significant viremia, which resulted in massive virus replication in B and T lymphocytes in lymphoid tissues and viral dissemination to the skin and the submucosa of respiratory epithelia. Attenuated MV was rarely detected in lymphoid tissues, and when it was, only in isolated infected cells. Following aerosol inhalation, attenuated MV was detected at early time points in the upper respiratory tract, suggesting local virus replication. This contrasts with pathogenic MV, which invaded the upper respiratory tract only after the onset of viremia. This study shows that despite in vitro differences, attenuated and pathogenic MV show highly similar in vivo tropism in the lungs. However, systemic spread of attenuated MV is restricted.